P570: REAL-WORLD EFFICACY OUTCOMES OF VENETOCLAX PLUS AZACITIDINE VS INTENSIVE CHEMOTHERAPY FOR INDUCTION THERAPY IN ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA
Authors: A. M. Zeidan, D. A. Pollyea, U. Borate, A. Vasconcelos, R. Potluri, D. Rotter, Z. Kiendrebeogo, L. Gaugler, G. Bonifacio, T. Prebet, C. Chen
Journal: HemaSphere (2022)

Background: Intensive chemotherapy (IC) is commonly used to achieve remission in patients with newly diagnosed acute myeloid leukemia (AML), although the relapse rate remains high. The combination of venetoclax, a BCL2 inhibitor, plus intravenous or subcutaneous azacitidine (ie, VEN-AZA), is FDA- and EMA-approved for the treatment of patients with newly diagnosed AML aged ≥ 75 years or with comorbidities that preclude the use of IC. Because of the challenging induction and maintenance decisions for some patients, it is important to understand the real-world patterns of use and outcomes of VEN-AZA vs IC. Aims: To compare US real-world outcomes for the use of VEN-AZA vs IC, particularly in older populations. Methods: This retrospective analysis was performed on a cohort of patients from the US-based Flatiron Health electronic health record-derived de-identified database, who had newly diagnosed AML and received induction therapy with VEN-AZA or IC between 21 Nov 2018 and 01 Jun 2021. Using an intention-to-treat analysis (including patients with less than 2 months of follow-up), patient groups were propensity score-matched in a 1:1 ratio using nearest neighbor matching with calipers set to 0.01 to reduce bias. Matched-patient assessments included morphological complete remission, overall survival (OS; defined as from first day of therapy to death), and relapse-free survival (RFS; from first day of therapy to relapse or death). Univariate analyses were used to investigate possible treatment-associated OS and RFS benefit in patient subgroups, including those with high-risk mutations. Results: Of 7484 patients in the Flatiron database with newly diagnosed AML, 1188 met the selection criteria and 436 were propensity score-matched resulting in 218 per treatment group. In the matched VEN-AZA vs IC cohorts, patients had a mean age of 69.9 vs 69.0 y and Charlson Comorbidity Index of 0.5 vs 0.7, respectively; 39% vs 38% were female. The rates of patients with complete remission (CR) and those with stem cell transplant (SCT) were significantly lower with VEN-AZA vs IC at 46% vs 62% (P=0.001) and 16% vs 31% (P<0.001), respectively. Fewer VEN-AZA– vs IC-treated patients received an early posttreatment bone marrow biopsy, with respective rates of 31% vs 69% (1 mo) and 57% vs 86% (2 mo). Median OS for VEN-AZA vs IC in the matched population was 13.0 vs 17.2 mo (P=0.263), respectively; it was 11.0 vs 15.6 mo (P=0.410) with censoring for SCT. Median RFS was numerically shorter for VEN-AZA than for IC (9.5 vs 11.0 mo; P=0.689); when including censoring for SCT, RFS was longer for VEN-AZA (7.5 vs 5.7 mo; P=0.027). Among subgroups, including those with high-risk mutations, no significant factor was found to be associated with OS in the matched patients (Figure). The frequency of known patients with high-risk mutations in RUNX1, ASXL1, and TP53 was similar for both treatment groups. Similar subgroup results were observed for RFS. Image:Summary/Conclusion: Rates of CR and SCT were significantly higher with IC. OS was nominally longer with IC vs VEN-AZA, with and without censoring for SCT; differences were not statistically significant. None of the subgroups tested, including patients with high-risk mutations, showed a significant OS association. Longer follow-up time may contribute to better characterized outcomes achieved with IC vs VEN-AZA in routine clinical practice. These data support more investigation on strategies to improve survival outcomes, including the impact of maintenance therapy.